The sense of sight involves receiving and focusing electromagnetic energy in the visible spectrum onto a retina of an eye, which converts the electromagnetic energy into signals that can be processed by the nervous system. The process by which photons of light are converted includes a cyclic decomposition and reconstitution of various proteins and enzymes within the photoreceptor cells of the retina. The photoreceptor cells include an opsin (e.g., rhodopsin in rod cells or photopsin in cone cells) bound to 11-cis retinal, a photosensitive derivative of vitamin A. Energy from incident light converts the 11-cis retinal to a different configuration, all-trans retinal, which changes the conformation of the opsin, leading to signal transduction. As a result, the opsin progressively breaks up into a number of intermediate compounds (e.g., metarhodopsin II and metarhodopsin III). For the photoreceptor cells to be able to respond to new light, the opsin needs to be reconstituted. The retinal pigment epithelium cells play a substantial role in the reconstitution by receiving the all-trans retinal from the photoreceptor cells and returning 11-cis retinal, which then recombines with an opsin to form new, functional visual pigment molecules. The retina is constantly exposed to light, requiring constant refreshing of the eyes to maintain functionality. Thus, the photoreceptor cells ability to be “recharged” by the retinal pigment epithelium cells is fundamental and indispensible to the sense of sight.
Unfortunately, a number of retinal diseases and conditions can cause failure or loss of photoreceptor cell or retinal pigment epithelium functionality, leading to significant loss of visual ability or even blindness. For example, age-related macular degeneration, geographic atrophy, retinitis pigmentosa, stargardt disease, macular telangiectasia, and other diseases have been known or are believed to cause failure or loss of photoreceptor or retinal pigment epithelium functionality are all retinal diseases that affect the functionality of the photoreceptor cell or retinal pigment epithelium cells. For some diseases, there is no device that can provide adequate assessment of the health and functionality of the photoreceptors and retinal pigment epithelium cells. This has severely hindered the advancement of research, classification, diagnosis, treatment, and patient management in connection with retinal diseases and conditions. For other diseases, present assessment techniques may be minimally adequate and could greatly benefit from new techniques providing more fine-grained analysis of disease pathogenesis, evaluation of treatment efficacies, and quantitative management of disease patients.
In particular, for example, age-related macular degeneration is a major public health problem. It destroys a patient's sharp and central vision in and around the macular region, significantly impacting the patient's ability to perform everyday activities (e.g., reading, driving, facial recognition, etc.) and degrading the patient's quality of life. Age-related macular degeneration currently affects over eight million people in the United States and is the leading cause of vision loss for people over 60 years old. As the aging population grows, the occurrence of age-related macular degeneration is expected to increase by over 50% by 2020. Not only will patients' suffer, a significant burden may also be imposed on society, for example, due to patients' loss of independence, rising health care costs associated with age-related macular degeneration medical expenses, and injuries (e.g., falling due to poor vision).
Currently, age-related macular degeneration is classified into two forms—a dry form (nonexudative) and a wet form (exudative). In the wet form of age-related macular degeneration, a patient's newly grown and fragile blood vessels leak blood into the retina, prohibiting clear viewing and/or damaging the retina, and potentially causing the retina to become detached from the choroid. In the dry form, drusen (i.e., yellow cellular deposits) accumulate between the retina and the choroid, causing atrophy of the retinal pigment epithelial cells and vision loss through the loss of photoceptor cells in the central part of the eye. Depending on the stage of the disease, the patient's vision may not change, become blurred, and/or become dark in areas. While treatments have been developed for the wet form of age-related macular degeneration (e.g., laser surgery, photodynamic therapy, and anti-VEGF injunctions), there is presently no FDA-approved treatment for the dry form of age-related macular degeneration.
At present, little is known about the causes of diseases such as age-related macular degeneration. The symptoms associated with age-related macular degeneration vary greatly and a number of different genes have been identified as potentially related to age-related macular degeneration. One hypothesis is that age-related macular degeneration is actually a group of retinal diseases. Currently, the presence of drusen is considered the clinical hallmark of dry form age-related macular degeneration. However, such diagnosis and classification is not adequate because the presence of drusen is ubiquitous for people over 50 years old and is considered to be associated with the natural aging process. Accordingly, only considering the presence and amount of drusen is inadequate for researching, classifying, diagnosing or treating the disease.
Indeed, there is no adequate system or method for researching, classifying, diagnosing or treating the age-related macular degeneration. The conventional fundus photography device is most widely used to provide a clear and color image of the retina and exam legions. However, because drusen is a part of the natural aging process, fundus photography images of drusen alone is not sufficient for complicated diseases such as age-related macular degeneration. Fluorescent angiography is a standard technique for detecting excess growth and/or leakage of blood vessels on the retina. While this technique is useful in the context of wet form age-related macular degeneration, it has little applicability to other diseases such as, for example, dry form age-related macular degeneration.
Optical coherence tomography is an emerging noninvasive retina imaging technology that can provide a three-dimensional view of the retinal structures using reflected light. It has been used to monitor the progress and to treat the wet form of age-related macular degeneration. However, optical coherence tomography can be sensitive to the change of the retinal structures and is not specific to the function of the retina. Although a functional optical coherence tomography technique has been developed, its sensitivity is low and its specificity to the retina health is unclear.
Another technique that has been attempted utilizes autofluorescence. In particular, autofluorescence of lipofuscin accumulation in retinal pigment epithelium cells was used to mark the stress levels of the retinal pigment epithelium cells. Although this technique may be informative, recent histology studies show that the autofluorescence of retinal pigment epithelium cells is not necessarily correlated with the loss of photoreceptor cells. It was found that the low level of autofluorescence may represent either healthy or completely dead retinal pigment epithelium cells, and a retina with a high level of autofluorescence may still have functioning photoreceptor and retinal pigment epithelium cells.